Immunogenic Cell Death: An Emerging Target in Gastrointestinal Cancers

Cells. 2022 Sep 28;11(19):3033. doi: 10.3390/cells11193033.

Abstract

Immunogenic cell death (ICD) is a regulated form of cell death that induces the activation of both innate and adaptive immune responses through the release of damage-associated molecular patterns (DAMPs) and their subsequent recognition by pattern-recognition receptors (PRRs), generating specific CD8+ T lymphocytes. Thus, ICD inducers (such as certain chemotherapeutic agents, targeted therapies, radiation, and oncolytic viruses) could become a potential cancer treatment by providing antitumour immunity and cancer vaccination. Moreover, their combination with immunotherapy, especially with immune checkpoint inhibitors, could overcome the immunosuppressive tumour microenvironment that characterises certain cancers, including gastrointestinal cancers. This review will provide insights into the role of ICD induction in colorectal, gastric, pancreatic, and hepatocellular carcinomas. Specifically, we will discuss the main mechanisms involved in ICD, their potential application in gastrointestinal cancer treatment, and the latest clinical trial updates.

Keywords: DAMPs; HMGB-1; colorectal cancer; gastric cancer; gastrointestinal cancers; hepatocellular carcinoma; immunogenic cell death; pancreatic cancer.

Publication types

  • Review
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents* / pharmacology
  • Clinical Trials as Topic
  • Gastrointestinal Neoplasms* / drug therapy
  • Humans
  • Immune Checkpoint Inhibitors
  • Immunogenic Cell Death
  • Immunotherapy
  • Oncolytic Viruses*
  • Tumor Microenvironment

Substances

  • Antineoplastic Agents
  • Immune Checkpoint Inhibitors

Grants and funding

This work was supported by the AIRC IG grant number 26330 to G.T., My First AIRC Grant “Luigi Bonatti e Anna Maria Bonatti Rocca” grant number 23681 to C.C., Convenzione Gemelli-FIMP Progetto CUP J38D19000690001 to G.T. and Ministry of Health CO 2019-12369662 to G.T.